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ERC-AG - ERC Advanced Grant

Objective

Since living memory, the basic treatment strategies for the therapy of human diseases has not much changed conceptually. Although the molecular understanding of metabolic disorders continues to progress significantly the therapeutic strategy is still based on specific, often heterologous compounds which interfere with critical disease targets, trigger a metabolic bypass reaction or complement a molecular deficiency. As systems biology is revealing gene-function correlations and metabolic network dynamics at great pace and synthetic biology enables bottom-up de-novo design of genetic devices with predictable behaviour, time has now come to develop novel treatment strategies. Prosthetic genetic networks are expected to play a central part of such future treatment strategies. Prosthetic networks are synthetic sensor/effector devices or molecular prostheses which, upon integration into cells and functional connection to their metabolism, monitor disease-relevant metabolites, process off-level concentrations and coordinate adjusted diagnostic, preventive or therapeutic responses in a seamless, automatic and self-sufficient manner. Using a synthetic biology approach and capitalizing on our pioneering prosthetic network designed to control urate homeostasis and treat the tumour lysis syndrome as well as gouty arthritis, ProNet is a highly integrated, multiparallel and interdisciplinary effort to provide a series of prosthetic sensor/effector circuits for precise trigger-control of therapeutic transgenes. ProNet will focus on providing novel treatment opportunities for diabetes and obesity, two core pathologies of the metabolic syndrome, which is on its way to become the top epidemic of the 21st century. ProNet may provide new opportunities for the treatment strategies of the future thereby making the classic therapy of taking pills and getting injections in specified amounts and at particular times likely to become a thing of the past.